Fully portable and wireless universal brain-machine interfaces enabled by flexible scalp electronics and deep-learning algorithm

Variation in human brains creates difficulty in implementing electroencephalography (EEG) into universal brain-machine interfaces (BMI). Conventional EEG systems typically suffer from motion artifacts, extensive preparation time, and bulky equipment, while existing EEG classification methods require training on a per-subject or per-session basis. Here, we introduce a fully portable, wireless, flexible scalp electronic system, incorporating a set of dry electrodes and flexible membrane circuit. Time domain analysis using convolutional neural networks allows for an accurate, real-time classification of steady-state visually evoked potentials on the occipital lobe. Simultaneous comparison of EEG signals with two commercial systems captures the improved performance of the flexible electronics with significant reduction of noise and electromagnetic interference. The two-channel scalp electronic system achieves a high information transfer rate (122.1 ± 3.53 bits per minute) with six human subjects, allowing for a wireless, real-time, universal EEG classification for an electronic wheelchair, motorized vehicle, and keyboard-less presentation

Food Security : Threats and Challenges of Sustainable Paddy Production in Sarawak

Rice is a staple food in Malaysia, hence paddy farming is vital to Malaysian households. However, the total amount of local rice output is still insufficient to meet household demand. There are several areas in Sarawak that are excellent for agriculture, particularly paddy growing. To maximise productivity, this potential agricultural area had not yet been used to its full potential. This study aims to highlight the challenges and threats facing Sarawak's paddy cultivation. This study collects qualitative information and contrasts findings from Sarawak's rural and sub-urban paddy farming. Interviews with 30 farmers were done in the sub-urban areas of Lundu and Siburan as well as the rural production areas of Bario and Long Seridan. Thematic analysis has been used to analyse the data. The results show that threats to and challenges to the sustainable production of the paddy sector include subsidies, a lack of understanding of the enhancement programme, a lack of communication channels to inform about production issues, a lack of marketing channels for the products, and other problems like price, ageing factors, and others. In the study, some suggestions for improving the sector will be found

MultiRes Attention Deep Learning Approach for Abdominal Fat Compartment Segmentation and Quantification

Global increase in obesity has led to alarming rise in co-morbidities leading to deteriorated quality of life. Obesity phenotyping benefits profiling and management of the condition but warrants accurate quantification of fat compartments. Manual quantification MR scans are time consuming and laborious. Hence, many studies rely on semi/automatic methods for quantification of abdominal fat compartments. We propose a MultiRes-Attention U-Net with hybrid loss function for segmentation of different abdominal fata compartments namely (i) Superficial subcutaneous adipose tissue (SSAT), (ii) Deep subcutaneous adipose tissue (DSAT), and (iii) Visceral adipose tissue (VAT) using abdominal MR scans. MultiRes block, ResAtt-Path, and attention gates can handle shape, scale, and heterogeneity in the data. Dataset involved MR scans from 190 community-dwelling older adults (mainly Chinese, 69.5% females) with mean age—67.85 ± 7.90 years), BMI 23.75 ± 3.65 kg/m2. Twenty-six datasets were manually segmented to generate the ground truth. Data augmentations were performed using MR data acquisition variations. Training and validation were performed on 105 datasets, while testing was conducted on 25 datasets. Median Dice scores were 0.97 for SSAT & DSAT and 0.96 for VAT, and mean Hausdorff distance was <5 mm for all the three fat compartments. Further, MultiRes-Attention U-Net was tested on a new 190 datasets (unseen during training; upper & lower abdomen scans with different resolution), which yielded accurate results. MultiRes-Attention U-Net significantly improved the performance over MultiResUNet, showed excellent generalization and holds promise for body-profiling in large cohort studies

Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15.

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic-pituitary-adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15 -/- mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies

GDF15 mediates the effects of metformin on body weight and energy balance.

Metformin, the world's most prescribed anti-diabetic drug, is also effective in preventing type 2 diabetes in people at high risk1,2. More than 60% of this effect is attributable to the ability of metformin to lower body weight in a sustained manner3. The molecular mechanisms by which metformin lowers body weight are unknown. Here we show-in two independent randomized controlled clinical trials-that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor. In wild-type mice, oral metformin increased circulating GDF15, with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to a high-fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GDNF family receptor α-like (GFRAL). In obese mice on a high-fat diet, the effects of metformin to reduce body weight were reversed by a GFRAL-antagonist antibody. Metformin had effects on both energy intake and energy expenditure that were dependent on GDF15, but retained its ability to lower circulating glucose levels in the absence of GDF15 activity. In summary, metformin elevates circulating levels of GDF15, which is necessary to obtain its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent

Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.RNA-sequencing was undertaken at the CRUK Cambridge Institute Genomics Core. Cell sorting was performed at the NIHR Cambridge BRC Cell Phenotyping Hub. PL received a Society for Endocrinology Early Career Grant. GR received an Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69] and a Royal College of Surgeons Research Fellowship. The work was partially funded by a project grant from the EFSD/Novo Nordisk Programme for Diabetes Research in Europe

Undiagnosed cardiovascular risk factors including elevated lipoprotein(a) in patients with ischaemic heart disease

ObjectivesThis study aims to investigate the prevalence of undiagnosed cardiovascular risk factors in patients with ischaemic heart disease (IHD).MethodsWe assessed the prevalence of previously undiagnosed cardiovascular risk factors, including elevated lipoprotein(a) [Lp(a)], among consenting patients with IHD who were admitted to hospital. Clinical information, including dietary history, from patients with newly diagnosed IHD and known IHD were compared.ResultsOf the 555 patients, 82.3% were males and 48.5% of Chinese ethnicity. Overall, 13.3% were newly diagnosed with hypertension, 14.8% with hypercholesterolemia, and 5% with type 2 diabetes (T2DM). Patients with newly diagnosed IHD, compared to those with known IHD, had a higher prevalence of new diagnoses of hypercholesterolemia (29.1% vs. 2.0%, p &lt; 0.001), hypertension (24.5% vs. 3.4%, p &lt; 0.001) and T2DM (7.3% vs. 3.1%, p = 0.023). Active smoking was prevalent in 28.3% of patients, and higher in newly diagnosed IHD (34.1% vs. 23.2%, p = 0.005). Elevated Lp(a) of ≥120 nmol/L was detected in 15.6% of all patients, none of whom were previously diagnosed. Dietary habits of &gt;50% of patients in both groups did not meet national recommendations for fruits, vegetables, wholegrain and oily fish intake. However, patients with known IHD had a more regular omega-3 supplement intake (23.4% vs. 10.3%, p = 0.024).ConclusionIncreased detection efforts is necessary to diagnose chronic metabolic diseases (hypertension, hypercholesterolemia, T2DM) especially among patients at high risk for IHD. Cardiovascular risk factors, in particular elevated Lp(a), smoking, and suboptimal dietary intake in patients with IHD deserve further attention

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion in the huntingtin (htt) gene. We found that peroxisome proliferator-activated receptor delta (PPARδ) interacts with htt and that mutant htt represses PPARδ-mediated transactivation. Increased PPARδ transactivation ameliorated mitochondrial dysfunction and improved cell survival of HD neurons. Expression of dominant-negative PPARδ in CNS was sufficient to induce motor dysfunction, neurodegeneration, mitochondrial abnormalities, and transcriptional alterations that recapitulated HD-like phenotypes. Expression of dominant-negative PPARδ specifically in the striatum of medium spiny neurons in mice yielded HD-like motor phenotypes, accompanied by striatal neuron loss. In mouse models of HD, pharmacologic activation of PPAR δ, using the agonist KD3010, improved motor function, reduced neurodegeneration, and increased survival. PPAR δ activation also reduced htt-induced neurotoxicity in vitro and in medium spiny-like neurons generated from human HD stem cells, indicating that PPAR δ activation may be beneficial in individuals with HD and related disorders